Role of SLC7A11/xCT in Ovarian Cancer

Fantone, Sonia; Piani, Federica; Olivieri, Fabiola; Rippo, Maria Rita; Sirico, Angelo; Di Simone, Nicoletta; Marzioni, Daniela; Tossetta, Giovanni

doi:10.3390/ijms25010587

Cited by 38 publications

(3 citation statements)

References 126 publications

(156 reference statements)

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“…Interestingly, the effect of ATF4 on NRF2 is also mediated by a cystine/glutamate antiporter (i.e., SLC27A11) [30]. The role of the protein coded by SLC7A11 is not clear in mammary tissue; however, it has been implicated in the maintenance of intracellular glutathione levels and chemotherapeutic resistance in both ovarian [36] and lung cells [37]. Furthermore, an increase in the expression of amino acid transporters can benefit milk protein synthesis [38], although this amino acid transporter was the only one upregulated by SFN (see Supplementary File S1).…”

Section: Gene Targets Of Nrf2 In Mact Cellsmentioning

confidence: 99%

The Experimental and In Silico-Based Evaluation of NRF2 Modulators, Sulforaphane and Brusatol, on the Transcriptome of Immortalized Bovine Mammary Alveolar Cells

Ford,

Bionaz

2024

IJMS

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Changes during the production cycle of dairy cattle can leave these animals susceptible to oxidative stress and reduced antioxidant health. In particular, the periparturient period, when dairy cows must rapidly adapt to the sudden metabolic demands of lactation, is a period when the production of damaging free radicals can overwhelm the natural antioxidant systems, potentially leading to tissue damage and reduced milk production. Central to the protection against free radical damage and antioxidant defense is the transcription factor NRF2, which activates an array of genes associated with antioxidant functions and cell survival. The objective of this study was to evaluate the effect that two natural NRF2 modulators, the NRF2 agonist sulforaphane (SFN) and the antagonist brusatol (BRU), have on the transcriptome of immortalized bovine mammary alveolar cells (MACT) using both the RT-qPCR of putative NRF2 target genes, as well as RNA sequencing approaches. The treatment of cells with SFN resulted in the activation of many putative NRF2 target genes and the upregulation of genes associated with pathways involved in cell survival, metabolism, and antioxidant function while suppressing the expression of genes related to cellular senescence and DNA repair. In contrast, the treatment of cells with BRU resulted in the upregulation of genes associated with inflammation, cellular stress, and apoptosis while suppressing the transcription of genes involved in various metabolic processes. The analysis also revealed several novel putative NRF2 target genes in bovine. In conclusion, these data indicate that the treatment of cells with SFN and BRU may be effective at modulating the NRF2 transcriptional network, but additional effects associated with cellular stress and metabolism may complicate the effectiveness of these compounds to improve antioxidant health in dairy cattle via nutrigenomic approaches.

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Section: Gene Targets Of Nrf2 In Mact Cellsmentioning

confidence: 99%

The Experimental and In Silico-Based Evaluation of NRF2 Modulators, Sulforaphane and Brusatol, on the Transcriptome of Immortalized Bovine Mammary Alveolar Cells

Ford,

Bionaz

2024

IJMS

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“…Changes in the levels of GSH, the essential coenzyme of GPX4, directly affect the enzyme’s ability to reduce lipid hydroperoxides, thus influencing its antioxidant capacity and the regulation of ferroptosis ( Endale and Mengstie, 2023 ). Therefore, the overexpression of SLC7A11 in ovarian cancer cells enhances GPX4 activity by increasing GSH levels, which assists cells in resisting ferroptosis and promotes cancer cell proliferation, invasion, and chemoresistance ( Fantone et al, 2024 ). Qin et al (2023) also reported that SLC7A11 protein levels were significantly greater in cisplatin-resistant A2780/DDP and SKOV3/DDP ovarian cancer cell lines than in their cisplatin-sensitive counterparts.…”

Section: Reversing Chemoresistance In Gynecological Malignancies Thro...mentioning

confidence: 99%

Ferroptosis: a novel strategy to overcome chemoresistance in gynecological malignancies

Xu,

Zheng,

Wang

et al. 2024

Front. Cell Dev. Biol.

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Ferroptosis is an iron-dependent form of cell death, distinct from apoptosis, necrosis, and autophagy, and is characterized by altered iron homeostasis, reduced defense against oxidative stress, and increased lipid peroxidation. Extensive research has demonstrated that ferroptosis plays a crucial role in the treatment of gynecological malignancies, offering new strategies for cancer prevention and therapy. However, chemotherapy resistance poses an urgent challenge, significantly hindering therapeutic efficacy. Increasing evidence suggests that inducing ferroptosis can reverse tumor resistance to chemotherapy. This article reviews the mechanisms of ferroptosis and discusses its potential in reversing chemotherapy resistance in gynecological cancers. We summarized three critical pathways in regulating ferroptosis: the regulation of glutathione peroxidase 4 (GPX4), iron metabolism, and lipid peroxidation pathways, considering their prospects and challenges as strategies to reverse chemotherapy resistance. These studies provide a fresh perspective for future cancer treatment modalities.

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“…Serous ovarian cancer, divided into low-grade and high-grade carcinoma, is one of the most frequently diagnosed ovarian epithelial carcinomas [2]. The biological behavior of high-grade serous ovarian cancer, such as rapid growth, high aggressiveness, and chemoresistance, often leads to poor prognosis for patient survival [2]; thus, new therapeutic targets for ovarian cancer treatment are needed [3]. Currently, keen attention is paid to the discovery of rapid screening tests for ovarian cancer and the development of new targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Primary Ovarian Cancer Cells and Established Cell Lines as a New Tool for Studies on Ovarian Cancer Cell Complexity

Szyposzynska,

Bielawska-Pohl,

Paprocka

et al. 2024

IJMS

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Primary cancer cells reflect the genetic background and phenotype of a tumor. Immortalized cells with higher proliferation activity have an advantage over primary cells. The aim of the study was to immortalize the primary ovarian cancer (OvCa) cells using the plasmid-carrying human telomerase reverse transcriptase (hTERT) gene and compare their phenotype and biological activity with the primary cells. The primary OvCa3 A and OvCa7 A cells were isolated from the ascitic fluid of two high-grade serous ovarian cancer patients and were characterized using immunocytochemical methods, flow cytometry, real-time RT-PCR, Western blot, metabolic activity, and migratory potential. Both immortalized ovarian cancer cell lines mirrored the phenotype of primary cancer cells, albeit with modifications. The OvCa3 A hTERT cells kept the mesenchymal stem cell phenotype of CD73/CD90/CD105-positivity and were CD133-negative, whereas the cell population of OvCa7 A hTERT lost CD73 expression, but almost 90% of cells expressed the CD133 characteristic for the CSCs phenotype. Immortalized OvCa cells differed in gene expression level with respect to Sox2 and Oct4, which was associated with stemness properties. The OvCa7 A hTERT cells showed higher metabolic and migratory activity and ALDH1 expression than the corresponding primary OvCa cells. Both primary and immortalized cell lines were able to form spheroids. The newly established unique immortalized cell line OvCa7 A hTERT, with the characteristic of a serous ovarian cancer malignancy feature, and with the accumulation of the p53, Pax8, and overexpression of the CD133 and CD44 molecules, may be a useful tool for research on therapeutic approaches, especially those targeting CSCs in ovarian cancer and in preclinical 2D and 3D models.

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Role of SLC7A11/xCT in Ovarian Cancer

Cited by 38 publications

References 126 publications

The Experimental and In Silico-Based Evaluation of NRF2 Modulators, Sulforaphane and Brusatol, on the Transcriptome of Immortalized Bovine Mammary Alveolar Cells

The Experimental and In Silico-Based Evaluation of NRF2 Modulators, Sulforaphane and Brusatol, on the Transcriptome of Immortalized Bovine Mammary Alveolar Cells

Ferroptosis: a novel strategy to overcome chemoresistance in gynecological malignancies

Comparative Analysis of Primary Ovarian Cancer Cells and Established Cell Lines as a New Tool for Studies on Ovarian Cancer Cell Complexity

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